Bbackground Familial hypercholesterolemia (FH) is, an autosomal dominant disorder of lipoprotein metabolism which can lead to premature coronary heart disease (pCHD)., is mainly caused by mutations in the low-density lipoprotein receptor (LDLR) gene. according to the Dutch Lipid Clinic Network criteria. There are about 3.8 million potential FH patients in China, whereas the clinical and genetic data of FH are limited. In this study, genetic screening and functional analyses were conducted in 65 Chinese clinical definite FH patients in order to better understand FH pathogenicity and the mechanism by which certain genetic mutations result in FH. Methods Dutch Lipid Clinic Network(DLCN) criteria was used to diagnose definite FH in the hypercholesterolemic outpatients with hypercholesterolemia. Resequencing chip analysis combined with Sanger sequencing validation were used to identify mutations in the five6 these clinical definite FH patients according to Dutch Lipid Clinic NetworkDLCN criteria according to the Dutch Lipid Clinic Network criteria. In silico analysis was conducted in mutations with unknown pathogeniciwith typreviously unknown pathogenicity. Then, the novel mutant receptors were transfected into human embryo kidney 293(HEK-293) cells. The binding and the internalization activities of the mutant receptorLDLRs novel mutation receptors were analyzed by flow cytometry. The prevalence of definite FH in hypercholesterolemia outpatients with hypercholesterolemiain in this study is 1.953.20%. Using genetic testing, oOne homozygous FH (HoFH), one heterozygous FH (HeFH) and 3 compound heterozygous FH patients were confirmed. 8 Eight mutations in Low-density lipoprotein receptor(the LDLR) gene were identified, in which c.357delG was a novel mutation and cosegregated with the FH phenotype. BFamily verification and bioinformatic analysis confirmed that c.357delG as was a pathogenic mutation. Furthermore, when compared with the wild-type LDLRs by flow cytometry analysis, the binding and internalization activities of c.357delG mutant LDLRs were reduced by 35% and 49%, respectively. Thus, the c.357delG mutation was likely the molecular mechanism underlying the etiology of FH in this family. Conclusions This study identified eight LDLR gene mutations in six five patients with clinicaldefinite definite Chinese FH probandspatients, in which c.357delG is a novel pathogenic mutation. These findings increase our understanding of the genetic spectrumbackground of FH in the Chinese populationa. © 2018 Science Press. All rights reserved.